I am currently Professor of Pharmacology and Psychiatry at the University of Texas Health Science Center at San Antonio where I have spent >75% of my time and effort on research supported by 5 R01s and a K02 award from NIDA. My goal in submitting a Research Career Award (RCA, K05) is to allow me to continue devoting >75% of my time to drug abuse research and training. Support under the RCA mechanism (K02) for the past 10 years has allowed me to avoid most teaching and service to the University and instead to devote my time to developing a preclinical research laboratory that focuses on the behavioral and pharmacologic determinants of drug abuse, dependence and withdrawal. I also have had the freedom to pursue several new and productive collaborations on this campus and elsewhere and I have spent considerable time training and promoting the careers of young researchers. This revised application is submitted in response to PA-00-21 "Senior Scientist Award." The major scientific goals of my career development during the period for which support is requested are the following: to understand the neuropharmacologic mechanisms that mediate the dependence and withdrawal effects of opioids and benzodiazepines; to identify the mechanisms that contribute to the therapeutic as well as abuse related effects of GHB and related compounds, in part, through the discovery of new compounds; to determine how insulin-receptor pathways in brain modulate behavioral actions of stimulants; to expand research capabilities of our group to include in vivo voltammetry, genomics, and behavioral studies in mice; and to continue a major commitment to collaborations and training of young investigators in drug abuse research. Major goals for the next several years also include submission of an institutional pre- and postdoctoral training grant, work towards obtaining resources for the expansion and further renovation of our laboratory facilities, in part through the establishment of a Center of Excellence in Behavioral Pharmacology, and continued recruitment of students, particularly underrepresented minorities from South Texas, to our graduate program in pharmacology, especially the behavioral sciences. My Chairman, Dr. Frazer, and the Administration are committed to the continued growth of drug abuse research at this institution, as evidenced by their financial commitments through the recruitment of a new investigators and providing matching funding for the renovation of laboratory animal facilities. This award will allow me to continue spending the majority of my time on NIH-sponsored research and on the expansion of drug abuse research and training at the Health Science Center.